title: Changing frequency of equivocal HER-2/neu scores and factors predictive of negative HER 2/neu fluorescent in situ hybridisation in invasive carcinomas of the breast.
abstract: BACKGROUND
  Analysis of human epidermal growth factor receptor 2 (HER-2) status has become standard of care in breast cancer patients due to its important prognostic and therapeutic implications. Immunohistochemistry (IHC) is the most commonly used primary method for detection of HER-2 overexpression. Controversy exists on the interpretation of samples that are equivocal for HER 2 status (IHC 2+). Recent guidelines state that samples equivocal for HER 2 status require validation with fluorescent in situ hybridisation (FISH). The use of FISH, however, despite higher accuracy comes at a higher cost that is not affordable to all patients.
  
  
  METHODS
  This study is a retrospective study conducted at the American University of Beirut Medical Center, including women diagnosed with breast cancer with equivocal IHC scores presenting between 2009 and 2011. We attempted to correlate clinicopathological characteristics of patients diagnosed with breast cancer that can influence conclusions made on HER 2 status when analysing IHC equivocal samples in an effort to decrease the need for FISH testing. 113 patients in our records were included; charts were reviewed for different patient clinical characteristics and samples were analysed for pathological characteristics.
  
  
  RESULTS
  Using logistic regression, progesterone receptor status and HER-2 staining of the normal glands around the tumour by IHC were the two statistically significant variables that showed association with FISH results. The strength of progesterone receptor status positivity and HER-2 staining of the normal glands around the tumour were proportional to the likelihood of a negative FISH. Also, the presence of strong and diffuse hormone receptor positivity in low-grade tumours was predictive of negative HER-2 status.
  
  
  CONCLUSIONS
  In countries where resources are strained, oncologists need to think of measures to minimise the increasing financial burden of cancer care. Our study serves to highlight a few clinicopathological characteristics that might eliminate the need for further testing through FISH.
authors.affiliation: Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, , Beirut, Lebanon.
authors.forename: Fouad
authors.initials: F
authors.lastname: Boulos
authors.forename: Chantal G
authors.initials: CG
authors.lastname: Farra
authors.forename: Ehab M
authors.initials: EM
authors.lastname: Saad Aldin
authors.forename: Cleo
authors.initials: C
authors.lastname: Masaad
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Hassoun
authors.forename: Faysal
authors.initials: F
authors.lastname: Fedda
authors.forename: Hassan
authors.initials: H
authors.lastname: Doumiati
authors.forename: Ayman N
authors.initials: AN
authors.lastname: Tawil
authors.forename: Zeina
authors.initials: Z
authors.lastname: Nasser
authors.forename: Zeina
authors.initials: Z
authors.lastname: Nahleh
authors.forename: Arafat
authors.initials: A
authors.lastname: Tfayli
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007861:Lebanon; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: BREAST; CANCER; FISH; IMMUNOHISTOCHEMISTRY